Python Scripting, add hotkey with map type Mouse?
Shift+LMB example to toggle Properties > Scene > Simplify:

import bpy

# operator
class ToggleSimplify(bpy.types.Operator):
    bl_idname = "view3d.toggle_simplify"
    bl_label = "Toggle Simplify"
    bl_options = {'REGISTER', 'UNDO'}

    def execute(self, context):
        context.scene.render.use_simplify = not context.scene.render.use_simplify
        return {'FINISHED'}

addon_keymaps = []
# register
def register():
    bpy.utils.register_class(ToggleSimplify)

    # handle the keymap
    wm = bpy.context.window_manager
    kc = wm.keyconfigs.addon
    if kc:
        km = wm.keyconfigs.addon.keymaps.new(name='3D View', space_type='VIEW_3D')
        kmi = km.keymap_items.new(ToggleSimplify.bl_idname, type='LEFTMOUSE', value='PRESS', shift=True)
        addon_keymaps.append((km, kmi))

# unregister
def unregister():

    for km, kmi in addon_keymaps:
        km.keymap_items.remove(kmi)
    addon_keymaps.clear()

    bpy.utils.unregister_class(ToggleSimplify)

if __name__ == "__main__":
    register() 


Also see: https://www.blender.org/api/blender_python_api_current/bpy.types.KeyMapItems.html